Electrospray is a popular method of soft ionisation in mass spectrometry, since it allows the analysis of fluid samples pre-separated by liquid chromatography or capillary electrophoresis, the ionization of complex molecules without fragmentation, and a reduction in the mass-to-charge ratio of heavy molecules by multiple charging [Gaskell 1997].
The principle of electrospray is simple. A voltage is applied between an electrode typically consisting of a diaphragm containing an orifice and a capillary needle containing a liquid analyte. Liquid is extracted from the capillary tip and its free surface is drawn into a Taylor cone, from which large charged droplets are emitted. The droplets are accelerated to supersonic speed, evaporating as they travel. Coulomb repulsion of the charges in the shrinking droplet results in fragmentation to ions when the Rayleigh stability limit is reached. The resulting ions can be multiply charged.
Additional methods are used to promote a well-dispersed spray of small droplets and hence a concentrated flow of analyte ions. Often these are based on pneumatic nebulisation by a coaxial gas stream, and a variety of pneumatic nebulisers have been demonstrated [U.S. Pat. No. 4,746,068; Wachs 2001; U.S. Pat. No. 6,478,238]. Aerodynamic effects such as the Coanda and Venturi effects are also used to improve the efficiency of ion transmission towards the inlet of a subsequent analyser such as a mass spectrometer [WO 00/64591; U.S. Pat. No. 6,992,299].
In a conventional electrospray system, with capillaries of around 100 microns internal diameter, flow rates are of the order of 1 micro-litre per minute, and extraction voltages lie in the range 2.5 kV-4 kV. Flow rates and voltages are considerably reduced in so-called “nanospray systems” [Wilm 1996], based on capillaries having internal diameters ranging down to around 5 micron [U.S. Pat. No. 5,115,131; U.S. Pat. No. 5,788,166]. Decreasing the capillary diameter and lowering the flow rate also tends to create ions with higher mass-to-charge ratio.
Considerable progress has been made in integrating nanospray ionisation sources with chip-based separation devices. For example, an ion spray can be drawn from the edge of a glass chip containing a capillary electrophoretic separator [Ramsey 1997; U.S. Pat. No. 6,231,737]. Since then, similar sources have been demonstrated in many materials, especially plastics. Geometries in which the analyte flows through a capillary etched perpendicular to the surface of a silicon chip have also been demonstrated [Schultz 2000; U.S. Pat. No. 6,723,985]. Such devices may be formed into two-dimensional arrays, and it has been shown they can provide an increased ion-flux based on the ion streams derived from many separate nanospray sources [Tang 2001, U.S. Pat. No. 6,831,274]. Nebulisers have also been provided for chip-based nanospray sources, for use with integrated capillaries [Zhang 1999] and with inserted capillaries [Syms 2007]. However, pneumatic nebulisers have not so far been used with array-type sources, reducing the potential advantage of the use of an array.
Capillary electrospray sources have also been considered for use in so-called colloidal thrusters, a method of micro-propulsion or attitude adjustment of spacecraft based on the ejection of ions from capillaries [Mueller 1997; Muller 2002]. In some cases the devices have been micro-fabricated in silicon [U.S. Pat. No. 6,516,604].
The use of a capillary with a small internal diameter as a source for nanospray suffers from a number of disadvantages. These include the difficulty of fabricating suitably fine features, especially in an integrated device, the likelihood of clogging of such features by particulate matter or deposits, and problems with matching flow rates to pre-separation sources of liquid analyte such as liquid chromatography systems.
One solution to the problem of forming and using a capillary source with a very small internal diameter is to include a porous bead inside a larger capillary at its tip [U.S. Pat. No. 5,975,426]. Similarly, one solution to the problem of flow rate matching is to include inside the capillary a wick element containing an aggregate of parallel, wettable fibers [U.S. Pat. No. 6,297,499] or nanowires [U.S. Pat. No. 7,141,807].
While these solutions purport to address the aforementioned problems there is still a need for improved ionisation sources.